autonomic control of the circulation and vdr

Conditions: Venous Distension Reflex; Blood Pressure

Summary: the study objective of this project is to examine the mechanisms of the venous distension reflex (vdr) in humans. we hypothesize that cox blockade with ketorolac tromethamine, an intravenous nsaid, will attenuate the muscle sympathetic nerve activity (msna) response to limb venous distension. to gain further insight into whether the cox byproducts directly stimulate chemically-sensitive afferents, or enable venodilation and indirectly evoke afferent stimulation, we will measure vein size using 3t mri during venous distention with and without ketorolac infusions.

we will use a prospective observational design to examine if a cox blockade will inhibit the msna response to venous distension (aim1), and if a cox blockade will alter vein sizes during venous distension (aim2). each subject will serve as their own control. aim 1: an iv will be inserted in the antecubital fossa of one arm, and the wrist-to-elbow occlusion will be performed. to block the cox system, 6 mg ketorolac tromethamine in 10 ml saline will be infused into the forearm over 1 minute (infusion 1). after 10 minutes, a second infusion of ketorolac tromethamine (up to 3 mg) in 5% of the forearm volume of saline,( \~40-60 ml) will be infused into the occluded forearm at a rate of \~ 30 ml/min (infusion 2). five minutes of data will then be collected before releasing the upper arm cuff. infusion 1 is to block the cox pathway, while infusion 2 is to induce venous distension. in the saline control trial, saline (without ketorolac) in identical volumes as those in the cox blockade trial will be performed on a separate day. aim 2: the subject will lie supine inside the mri scanner. the subject will be instrumented with cuffs for the wrist-to-elbow occlusion procedure on one arm, and cuffs for automated bp and hr measurements from the other arm, the images will be obtained before and during the wrist-to-elbow occlusion procedure. the sizes of veins (i.e. cross sectional area) will be measured offline.

Eligibility criteria:
inclusion criteria * are capable of giving informed consent * are any race or ethnicity * are fluent in written and spoken english * have a satisfactory history and physical exam to meet inclusion/exclusion criteria * are free of acute or chronic medical conditions * are 21 - 35 years of age (inclusive) * weigh over 50 kg exclusion criteria * are less than 21 or over 35 years of age * are pregnant or nursing women * are prisoners or institutionalized individuals or unable to consent * any chronic diseases (hypertension, heart, lung, neuromuscular disease, kidney disease, diabetes or cancer). * are taking medications that may affect their cardiovascular or nervous system * has taken an nsaid within 48 hours of any visit (visit will need to be rescheduled) * has never taken nsaids and therefore would not know if they are allergic to it * have a supine bp \>140/90 mmhg * have known allergy to ibuprofen-like drugs (nsaids) or aspirin * have history of asthma or nasal polyps * have history of gi bleeding or ulcers * subjects with ferromagnetic metal implants * subjects who are claustrophobic